A novel animal model to study the association between alcohol abuse during late adolescence with common conditions observed in combat Veterans

The maturation of the prefrontal cortex (PFC) is a hallmark of the transition between adolescence to adulthood. Because the PFC matures around 25 years of age, it is safe to say that most frontline soldiers are still during adolescence. The Center of Disease Control and Prevention reports that service members have the highest alcohol use of all queried professions. Moreover, alcohol use increases following combat deployment. Therefore, most service members are exposed to large amounts of alcohol during a period that the PFC is still immature. The PFC acts through top-down control to regulate the activity of many subcortical regions; and doing so regulates and integrates emotional and stress responses, as well as motivation and reward seeking. Taking the aforementioned facts together we hypothesize that “consumption of constant and high levels of alcohol by service members, affects PFC development and makes these subjects more prone to develop conditions that afflict our Veterans such as: altered stress response, addiction, depression, mood swings and Post-traumatic stress disorder (PTSD). Testing this hypothesis and its underlying mechanisms in an appropriate animal model would make a great contribution to the field. Unfortunately, current animal models have limitations in studying consequences of chronic alcohol use restricted to late adolescence. For instance, rodents have a very short-late adolescence, making it difficult to mimic a chronic and heavy alcohol consumption. In non-human primates, “late adolescence” is too long making experiments very time consuming and costly. In this 3-year BLRD application, we propose to develop a novel animal model that can mimic prolonged heavy alcohol consumption restricted to late adolescence. Developing this model would pave the way to test how alcohol exposure during late adolescence can alter dopaminergic neurotransmission and stress responses - making the prefrontal cortex vulnerable to “second hits” such as high stress and Traumatic Brain Injury (TBI). This information could help us understand why Veterans are much vulnerable to mental health disorders and potentially devise therapeutic interventions.